Improving the understanding of healthcare-associated infections and developing interventions to prevent them are high priorities for the Department of Health and Human Services and its operating divisions: the NIH, the AHRQ, and the CDC. Central line-associated bloodstream infections (CLABSI) and infections due to multi-drug resistant organisms (MDRO) are among the most common healthcare-associated infections, and the most costly in terms of expenditure of healthcare resources and patient morbidity and mortality. Chlorhexidine gluconate (CHG) bathing has been shown to reduce the incidence of CLABSI and acquisition of MDRO (colonization and infection) in critically ill adults. It is unknown whether the same benefit can be expected in pediatric oncology patients. Studies in this population are urgently needed as these infections are potentially devastating, the pathogenesis of bloodstream infections may be different in this population, and there is heightened concern about skin integrity. The primary goal of this proposal is to determine whether CHG bathing reduces the incidence of CLABSI and acquisition of epidemiologically important MDRO in children with cancer. The secondary goal is to investigate reduced susceptibility to CHG in a clinical context. It is important to monitor for and understand the implications of resistance to antimicrobial and antiseptic interventions. In the case of CHG, there are limited cross-sectional and in vitro data suggesting that exposure to CHG may induce CHG resistance in bacteria, and that this resistance may be associated with resistance to commonly-used antibiotics. However, the clinical applicability of these data is uncertain. There are 3 Specific Aims: Aim 1. To determine whether CHG bathing decreases the incidence of CLABSI in children with cancer. Aim 2. To determine whether CHG bathing decreases new acquisition (colonization or infection) of epidemiologically important MDRO in children with cancer. Aim 3. To determine whether CHG bathing in children with cancer is associated with cutaneous bacterial isolates with reduced susceptibility to CHG. Strategy. We propose a randomized, double-blind, controlled trial of CHG bathing in children with cancer in collaboration with the Children's Oncology Group and 12 experienced Children's Oncology Group centers that are committed to the success of this study. Relevance. Results from this study will determine the effect of CHG bathing in reducing CLABSI and acquisition of MDRO in high-risk pediatric oncology patients. Such results have the potential to impact the clinical care and outcomes of these children. This study will also provide novel data about reduced susceptibility to CHG and the relationship between CHG susceptibility and resistance to commonly used antibiotics. These data may benefit future recipients of CHG bathing.